BALB/c mice injected with gamma-irradiated cells of some BALB/c myeloma tumors become immune to the tumors and produce cytotoxic T cells that lyse the tumor cells. Isolation of the responsible tumor-associated antigen (Ag) is complicated, because cytotoxic T cells seem obligated to recognize on their target cells both a relevant Ag and certain products of the major histocompatiblity complex (H-2 restriction). Because of this dual requirement, the traditional assay for monitoring the isolation of Ag (inhibition of the relevant Ab reaction) is unlikely to be effective: in H-2 restricted reactions soluble Ag alone is probably not inhibitory. Various model systems are described for investigating both a possible basis for H-2 restriction and some means for reconstituting with soluble Ags the H-2-dependent complex antigeneic structures recognized by cytotoxic T cells. A second line of investigation is aimed in the long-run at understanding the regulatory mechanisms that control production of particular immunoglobulin (Ig) isotypes (classes of heavy chains and types of ligh chains). These studies will focus initially on lambda 2, an unusual light chain present on a small proportion of mouse Igs. Mechanisms that suppress or enhance the production of lambda 2 chains will be investigated.